Journal ArticleDOI
Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting
Masahiro Kaneda,Masaki Okano,Kenichiro Hata,Takashi Sado,Takashi Sado,Takashi Sado,Naomi Tsujimoto,Naomi Tsujimoto,Naomi Tsujimoto,En Li,En Li,Hiroyuki Sasaki,Hiroyuki Sasaki +12 more
TLDR
Results indicate that both DnMT3a and Dnmt3L are required for methylation of most imprinted loci in germ cells, but also suggest the involvement of other factors.Abstract:
Imprinted genes are epigenetically marked during gametogenesis so that they are exclusively expressed from either the paternal or the maternal allele in offspring1 Imprinting prevents parthenogenesis in mammals and is often disrupted in congenital malformation syndromes, tumours and cloned animals1 Although de novo DNA methyltransferases of the Dnmt3 family are implicated in maternal imprinting2, the lethality of Dnmt3a and Dnmt3b knockout mice3 has precluded further studies We here report the disruption of Dnmt3a and Dnmt3b in germ cells, with their preservation in somatic cells, by conditional knockout technology4 Offspring from Dnmt3a conditional mutant females die in utero and lack methylation and allele-specific expression at all maternally imprinted loci examined Dnmt3a conditional mutant males show impaired spermatogenesis and lack methylation at two of three paternally imprinted loci examined in spermatogonia By contrast, Dnmt3b conditional mutants and their offspring show no apparent phenotype The phenotype of Dnmt3a conditional mutants is indistinguishable from that of Dnmt3L knockout mice2,5, except for the discrepancy in methylation at one locus These results indicate that both Dnmt3a and Dnmt3L are required for methylation of most imprinted loci in germ cells, but also suggest the involvement of other factorsread more
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References
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Journal ArticleDOI
DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development.
TL;DR: It is demonstrated that two recently identified DNA methyltransferases, DnMT3a and Dnmt3b, are essential for de novo methylation and for mouse development and play important roles in normal development and disease.
Journal ArticleDOI
Targeted mutation of the DNA methyltransferase gene results in embryonic lethality.
TL;DR: Results indicate that while a 3-fold reduction in levels of genomic m5C has no detectable effect on the viability or proliferation of ES cells in culture, a similar reduction of DNA methylation in embryos causes abnormal development and embryonic lethality.
Journal ArticleDOI
Genomic imprinting: parental influence on the genome
TL;DR: The study of imprinting provides new insights into epigenetic gene modification during development, and is thought to influence the transfer of nutrients to the fetus and the newborn from the mother.
Journal ArticleDOI
High sensitivity mapping of methylated cytosines.
TL;DR: A genomic sequencing technique which is capable of detecting every methylated cytosine on both strands of any target sequence, using DNA isolated from fewer than 100 cells is developed.
Journal ArticleDOI
Dnmt3L and the establishment of maternal genomic imprints.
TL;DR: Bisulfite genomic sequencing of DNA from oocytes and embryos showed that removal of Dnmt3L prevented methylation of sequences that are normally maternally methylated, and the defect was specific to imprinted regions, and global genome methylation levels were not affected.